TY - JOUR
T1 - High information content assays for genetic toxicology testing
T2 - A report the International Workshops on Genotoxicity Testing (IWGT)
AU - Dertinger, Stephen D.
AU - Totsuka, Yukari
AU - Bielas, Jason H.
AU - Doherty, Ann T.
AU - Kleinjans, Jos
AU - Honma, Masamitsu
AU - Marchetti, Francesco
AU - Schuler, Maik J.
AU - Thybaud, Veronique
AU - White, Paul
AU - Yauk, Carole L.
N1 - Publisher Copyright:
© 2019 Elsevier B.V.
PY - 2019/11
Y1 - 2019/11
N2 - We live in an era of 'big data', where the volume, velocity, and variety of the data being generated is increasingly influencing the way toxicological sciences are practiced. With this in mind, a workgroup was formed for the 2017 International Workshops on Genotoxicity Testing (IWGT) to consider the use of high information content data in genetic toxicology assessments. Presentations were given on adductomics, global transcriptional profiling, error-reduced single-molecule sequencing, and cellular phenotype-based assays, which were identified as methodologies that are relevant to present-day genetic toxicology assessments. Presenters and workgroup members discussed the state of the science for these methodologies, their potential use in genetic toxicology, current limitations, and the future work necessary to advance their utility and application. The session culminated with audience-assisted SWOT (strength, weakness, opportunities, and threats) analyses. The summary report described herein is structured similarly. A major conclusion of the workgroup is that while conventional regulatory genetic toxicology testing has served the public well over the last several decades, it does not provide the throughput that has become necessary in modern times, and it does not generate the mechanistic information that risk assessments ideally take into consideration. The high information content assay platforms that were discussed in this session, as well as others under development, have the potential to address aspect(s) of these issues and to meet new expectations in the field of genetic toxicology.
AB - We live in an era of 'big data', where the volume, velocity, and variety of the data being generated is increasingly influencing the way toxicological sciences are practiced. With this in mind, a workgroup was formed for the 2017 International Workshops on Genotoxicity Testing (IWGT) to consider the use of high information content data in genetic toxicology assessments. Presentations were given on adductomics, global transcriptional profiling, error-reduced single-molecule sequencing, and cellular phenotype-based assays, which were identified as methodologies that are relevant to present-day genetic toxicology assessments. Presenters and workgroup members discussed the state of the science for these methodologies, their potential use in genetic toxicology, current limitations, and the future work necessary to advance their utility and application. The session culminated with audience-assisted SWOT (strength, weakness, opportunities, and threats) analyses. The summary report described herein is structured similarly. A major conclusion of the workgroup is that while conventional regulatory genetic toxicology testing has served the public well over the last several decades, it does not provide the throughput that has become necessary in modern times, and it does not generate the mechanistic information that risk assessments ideally take into consideration. The high information content assay platforms that were discussed in this session, as well as others under development, have the potential to address aspect(s) of these issues and to meet new expectations in the field of genetic toxicology.
KW - Genetic toxicology
KW - Adductomics
KW - Transcriptomics
KW - Error-reduced sequencing
KW - High information content
KW - New technologies
KW - DISCRIMINATE RODENT CARCINOGENS
KW - INDUCED DNA-ADDUCTS
KW - TOXICOGENOMICS SIGNATURE
KW - NONGENOTOXIC CHEMICALS
KW - RARE MUTATIONS
KW - DAMAGE
KW - BIOMARKER
KW - BATTERY
KW - QUANTIFICATION
KW - NONCARCINOGENS
U2 - 10.1016/j.mrgentox.2019.02.003
DO - 10.1016/j.mrgentox.2019.02.003
M3 - Article
C2 - 31699343
SN - 1383-5718
VL - 847
JO - Mutation Research-Genetic Toxicology and Environmental Mutagenesis
JF - Mutation Research-Genetic Toxicology and Environmental Mutagenesis
M1 - 403022
ER -